Dr Nicola Oliver
Given the pace of change with ‘all things COVID’, it can be hard – even for those who follow all the updates – to know what the overall state of play is regarding medical developments in particular, as opposed to just the most recent news. In this new type of Bulletin, we provide a monthly view of what we think the medical state of play is. That said, the main uncertainty at the moment in considering future strategies is the ‘if and when’ of vaccines, and so this first update looks only at vaccines.
Introduction
Back in May, we described the state of play with regard to vaccine development to protect from the SARS-CoV-2 virus (link). At that time, several compounds were in phase 2 of the clinical trial process; most were in phase 1 or pre-clinical. Of most interest were those that had been partially developed and then shelved following the SARS outbreak in 2002.
As of 31 July, according to the World Health Organisation, (WHO), there are 26 candidate vaccines in clinical evaluation, (phases 1-3) (link). Of these, six are in phase 3 (the final stage of clinical testing in which safety and efficacy are tested). If successful, this will usually lead to application for approval.
The clinical trial process does not guarantee a final, approved product, even in those that reach the later stages. However, past experience of vaccine development adjusted by the immense pressure and funding to achieve success make us think that a declaration of phase 3 success for one vaccine is likely by end 2020 / early 2021.
If we do get to a final, approved product soon there are additional challenges to consider. The development of an effective vaccine is being widely heralded as a key milestone in combating the pandemic; here we present some concerns regarding this view.
Challenges
Effectiveness
SARS-CoV-2 is a novel virus and so there are many unanswered questions regarding, amongst many things, the generation and levels of antibodies in those who have been infected with it. Whilst some trials have reported the generation of strong immune responses in participants, it is not certain how sustained this response will be.
Furthermore, the pressure to expedite the clinical trial process could raise safety concerns. We should not rely on a future vaccine to be the holy grail of exiting from the necessary social distancing measures when we are still in the dark as to its effectiveness.
Manufacture
As mentioned, there are only a handful of candidate vaccines in the later stages of the clinical trial process. Following successful results, manufacturers will require regulatory approval. Clearly in a pandemic, this process will be shortened as much as possible; but bear in mind the mumps vaccine was the fastest-developed vaccine ever, and that took four years from start to finish.
A potential bottleneck will be scaling up production sufficiently to be able to vaccinate enough of the population to bring the pandemic under control. (There is also the real possibility that more than one vaccine shot will be required across a lifetime). Even if only half of the world’s population are willing, and able, to receive the vaccine (another hurdle), that is still a staggering 3½ billion doses that will need to be manufactured for a one-off dose.
We expect the time from approval to mass manufacture to be of the order of at least 6 months. However, that could be shorter for (eg) manufacture in the UK initially targetting key groups. Given the pressures, it is possible that pharmaceutical firms could start some production before phase 3 trial results are finalised.
Administration, uptake and acceptance
It is likely that an effective vaccine will be offered to the most vulnerable first, and to healthcare workers. It is possible that in the event of a successful phase 3 trial, emergency use vaccinations could commence to include healthcare works and vulnerable people. Following that, the challenge to vaccinate as many people as possible in as short a timeframe as possible will be on.
During the 2018/2019 influenza vaccination programme, 14 million doses were administered in England. It is likely that the vaccination programme for SARS-CoV-2 will be scaled up and ultimately offered to all age groups regardless of vulnerability.
Optimistically, if the vaccination programme was in progress throughout the year, and scaled up, then perhaps more than double could be administered each year through GP practices. In addition, some pharmacists already administer flu vaccines (one million doses in the 2018/2019 season), and this could increase administration capabilities. Widespread vaccine administration will take time.
The second factor here is acceptance and willingness to receive the vaccine. There is unfortunately a growing and vocal anti-vax movement, enabled by social media and the rapid dissemination of fake science with no evidence base.
Ironically, some of this is fuelled by the rapid pace of the vaccine development programme reported in the media; many vaccine opponents are seizing the potential safety concerns as a reason to avoid the vaccine altogether. More caution needs to be applied when reporting on vaccine development progress.
Conclusion
We cannot assume that an effective vaccine will be available (and utilised) at scale before mid-late 2021 and even that may be optimistic. We should therefore be acting in a way that assumes no effective vaccine in the short term for most people. Until that time, a new ‘normal’ should become part of our daily routines. Use of face coverings, sensible physical distancing, track and trace and localised protocols are essential.
As epidemiologist Mark Woolhouse at the University of Edinburgh, UK, told New Scientist in early April: “I do not think waiting for a vaccine should be dignified with the word ‘strategy’. It’s not a strategy, it’s a hope.”
